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a proteomic perspective of inbuilt viral protein regulation: pul46 tegument protein is targeted for degradation by icp0 during herpes simplex virus type 1 infection.much like the host cells they infect, viruses must also regulate their life cycles. herpes simples virus type 1 (hsv-1), a prominent human pathogen, uses a promoter-rich genome in conjunction with multiple viral trans-activating factors. following entry into host cells, the virion-associated outer tegument proteins pul46 and pul47 act to increase expression of viral immediate-early (α) genes, thereby helping initiate the infection life cycle. because pul46 has gone largely unstudied, we employed ...201323938468
biology of the tam receptors.the tam receptors--tyro3, axl, and mer--comprise a unique family of receptor tyrosine kinases, in that as a group they play no essential role in embryonic development. instead, they function as homeostatic regulators in adult tissues and organ systems that are subject to continuous challenge and renewal throughout life. their regulatory roles are prominent in the mature immune, reproductive, hematopoietic, vascular, and nervous systems. the tams and their ligands--gas6 and protein s--are essenti ...201324186067
norovirus genome circularization and efficient replication are facilitated by binding of pcbp2 and hnrnp a1.sequences and structures within the terminal genomic regions of plus-strand rna viruses are targets for the binding of host proteins that modulate functions such as translation, rna replication, and encapsidation. using murine norovirus 1 (mnv-1), we describe the presence of long-range rna-rna interactions that were stabilized by cellular proteins. the proteins potentially responsible for the stabilization were selected based on their ability to bind the mnv-1 genome and/or having been reported ...201323946460
directed evolution of a virus exclusively utilizing human epidermal growth factor receptor as the entry receptor.rational design and directed evolution are powerful tools to generate and improve protein function; however, their uses are mostly limited to enzyme and antibody engineering. here we describe a directed-evolution strategy, named the tandem selection and enrichment system (tses), and its use in generating virus with exclusive specificity for a particular cellular receptor. in tses, evolving viruses are sequentially and iteratively transferred between two different host cells, one for selection of ...201323926357
an easy operating pathogen microarray (eopm) platform for rapid screening of vertebrate pathogens.infectious diseases emerge frequently in china, partly because of its large and highly mobile population. therefore, a rapid and cost-effective pathogen screening method with broad coverage is required for prevention and control of infectious diseases. the availability of a large number of microbial genome sequences generated by conventional sanger sequencing and next generation sequencing has enabled the development of a high-throughput high-density microarray platform for rapid large-scale scr ...201324053492
hnrnp a1: the swiss army knife of gene expression.eukaryotic cells express a large variety of rna binding proteins (rbps), with diverse affinities and specificities towards target rnas. these proteins play a crucial role in almost every aspect of rna biogenesis, expression and function. the heterogeneous nuclear ribonucleoproteins (hnrnps) are a complex and diverse family of rna binding proteins. hnrnps display multiple functions in the processing of heterogeneous nuclear rnas into mature messenger rnas. hnrnp a1 is one of the most abundant and ...201324065100
towards the elements of successful insect rnai.rna interference (rnai), the sequence-specific suppression of gene expression, offers great opportunities for insect science, especially to analyze gene function, manage pest populations, and reduce disease pathogens. the accumulating body of literature on insect rnai has revealed that the efficiency of rnai varies between different species, the mode of rnai delivery, and the genes being targeted. there is also variation in the duration of transcript suppression. at present, we have a limited ca ...201324041495
systemic tumor-specific gene delivery.the objective of a systemically administered cancer gene therapy is to achieve gene expression that is isolated to the tumor tissue. unfortunately, viral systems have strong affinity for the liver, and delivery from non-viral cationic systems often results in high expression in the lungs. non-specific delivery to these organs must be overcome if tumors are to be aggressively treated with genes such as il-12 which activates a tumor immune response, and tnf-alpha which can induce tumor cell apopto ...201324035974
inhibition of arenavirus by a3, a pyrimidine biosynthesis inhibitor.arenaviruses merit significant interest as important human pathogens, since several of them cause severe hemorrhagic fever disease that is associated with high morbidity and significant mortality. currently, there are no fda-licensed arenavirus vaccines available, and current antiarenaviral therapy is limited to an off-labeled use of the nucleoside analog ribavirin, which has limited prophylactic efficacy. the pyrimidine biosynthesis inhibitor a3, which was identified in a high-throughput screen ...201324198417
previous exposure to an rna virus does not protect against subsequent infection in drosophila melanogaster.immune priming has been shown to occur in a wide array of invertebrate taxa, with individuals exposed to a pathogen showing increased protection upon subsequent exposure. however, the mechanisms underlying immune priming are poorly understood. the antiviral rnai response in drosophila melanogaster is an ideal candidate for providing a specific and acquired response to subsequent infection. we exposed d. melanogaster to two challenges of a virus known to produce an antiviral rnai response, to exa ...201324040086
induction of humoral and cellular immune responses against hepatitis c virus by vaccination with replicon particles derived from sindbis-like virus xj-160.a replication-defective, recombinant sindbis virus vector was utilized in a novel immunization strategy to induce humoral and cellular responses against hepatitis c virus (hcv). the recombinant vector, pvaxj-e1e2, expressing the gene for hcv glycoproteins e2 and e1, was constructed by inserting the e1e2 gene into the replicon pvaxj, a dna vector derived from sindbis-like virus xj-160. the defective replicon particles, xj-e1e2, were produced by transfecting bhk-21(e+capsid) cells, the packaging c ...201323250650
mcpip1 ribonuclease exhibits broad-spectrum antiviral effects through viral rna binding and degradation.monocyte chemoattractant protein 1-induced protein 1 (mcpip1), belonging to the mcpip family with highly conserved ccch-type zinc finger and nedd4-bp1, yacp nuclease domains, has been implicated in negative regulation of the cellular inflammatory responses. in this report, we demonstrate for the first time that this rna-binding nuclease also targets viral rna and possesses potent antiviral activities. overexpression of the human mcpip1, but not mcpip2, mcpip3 or mcpip4, inhibited japanese enceph ...201323355615
[updated inventory of mosquitoes (diptera: culicidae) of the island of la réunion, indian ocean].a literature analysis coupled with new entomological surveys conducted between 2009 and 2012 led to changes in the list of mosquito species present on the island of la réunion. using morphological criteria, orthopodomyia arboricollis is replaced by or. reunionensis. on the basis of morphometrical and genetic criteria, culex univittatus is replaced by cx. neavei. cx. poicilipes, which was already reported missing 40 years ago, has not been found again. anopheles arabiensis is confirmed as the onl ...201323681758
translation of viral mrnas that do not require eif4e is blocked by the inhibitor 4egi-1.high throughput screening has rendered new inhibitors of eukaryotic protein synthesis. one such molecule, 4egi-1 has been reported to selectively block the initiation factor eif4e. we have investigated the action of this inhibitor on translation directed by several viral mrnas which, in principle, do not utilize eif4e. we found that 4egi-1 inhibits translation directed by poliovirus ires, in rabbit reticulocyte lysates, to a similar extent as capped mrna. moreover, 4egi-1 inhibits translation dr ...201323870416
phosphorylation of eif2α is responsible for the failure of the picornavirus internal ribosome entry site to direct translation from sindbis virus replicons.translation directed by the poliovirus (pv) or encephalomyocarditis virus (emcv) internal ribosome entry site (ires) is very inefficient when expressed from sindbis virus (sv) replicons. this inhibition can be rescued by co-expression of pv 2a protease (2a(pro)). inhibition correlates with the extensive phosphorylation of eukaryotic initiation factor (eif) 2α induced by sv replication. confirmation that pv or emcv ires-driven translation can function when eif2α is not phosphorylated was obtained ...201323255624
specific nucleotide changes in the subgenomic promoter region influence infectivity of the sindbis virus.transcription of the subgenomic mrna of sindbis virus (sinv) is initiated at a subgenomic promoter (sp). alignment of sinv sequences identified a 68-nucleotide conserved domain spanning -19 to +49 relative to the subgenomic mrna start site. nucleotide t or c is present at -18 or +49 in all known sinvs while a sindbis-like virus xj-160 has an a or t at a corresponding position. our results indicate that deletion or substitution of the t at +49 decreased the activity of sp, while substituting t fo ...201323838061
recombination of replicon and helper rnas and the emergence of propagation-competent vectors upon sindbis virus vector production.sindbis vectors have shown remarkable antitumor efficacy and tumor-targeting capacity in animal models and hold promise for cancer therapy. different packaging systems are used to produce propagation-incompetent sindbis vectors. however, the vectors produced using either dh-bb single helper rna or split helper rna can spread in permissive cell cultures. we investigated the mechanisms of vector spreading and show, here, that recombination occurs between the replicon and dh-bb helper rna, leading ...201323716190
effect of larval density and sindbis virus infection on immune responses in aedes aegypti.stressful environmental conditions during mosquito larval development may enhance susceptibility of adult mosquitoes to viral pathogens. although anti-viral defense system in mosquitoes remains uncertain, stress-related enhancement of mosquito susceptibility to viral pathogens may be due to alteration of signaling pathways such as the toll and immune deficiency (imd) pathways. to test the influence of larval density and sindbis virus (sinv) infection on mosquito toll/imd pathways, 100 or 200 aed ...201323562781
requirements for eif4a and eif2 during translation of sindbis virus subgenomic mrna in vertebrate and invertebrate host cells.we have examined the requirements for the initiation factors (eifs) eif4a and eif2 to translate sindbis virus (sv) subgenomic mrna (sgmrna) in the natural hosts of sv: vertebrate and arthropod cells. notably, this viral mrna does not utilize eif4a in sv-infected mammalian cells. however, eif4a is required to translate this mrna in transfected cells. therefore, sv sgmrna exhibits a dual mechanism for translation with respect to the use of eif4a. interestingly, sv genomic mrna requires eif4a for t ...201323189929
climatic, ecological and socioeconomic factors as predictors of sindbis virus infections in finland.mosquito-borne sindbis virus (sinv) causes rash-arthritis syndrome in finland. major outbreaks with approximately 7-year cycles have caused substantial burden of illness. forest dwelling grouse are suspected to be amplifying hosts, with the infection transmitted to humans by mosquito bites. sinv infection surveillance data for 1984–2010 were used to create a negative binomial hurdle model, with seasonality, long-term cycles, climatic, ecological and socioeconomic variables. climatic factors duri ...201323158410
phenotypic and molecular characteristics of plaque-purified mx10 virus, an oriental-australian genotype of sindbis virus from yunnan, china.a previous investigation showed that mx10 virus, recently isolated in china, belongs to the oriental-australian (o/a) genotype of sindbis virus (sinv) (wang jinglin, 2011, atmh). similar to the mre16 isolate, the prototype o/a genotype of sinv, two derivate viruses with obviously different plaque morphologies were derived from mx10 virus, which were accordingly denoted as mx10-lp and mx10-sp. mx10-lp virus exhibited higher neurovirulence in neonatal mice than mx10-sp virus. analysis of the compl ...201322965578
[the concept of emerging viral diseases: what risk for reunion island?].in reunion island, the risk of emerging infectious diseases lies mainly in several viral zoonoses: west nile fever, sindbis virus, nipah virus, wesselsbron virus, rift valley fever and japanese encephalitis. there morbidity and consequences are more or less important but they all have a non-negligible epidemic potential, so they have to be monitored. indeed, the struggle against these emerging infectious diseases requires an early detection of the cases, thus a surveillance system capable of det ...201323765703
[construction and characterization of egfp reporter gene labeled sindbis virus].to construct and characterize egfp reporter gene labeled sindbis virus (sinv).201324319966
engineered alphavirus replicon vaccines based on known attenuated viral mutants show limited effects on immunogenicity.the immunogenicity of alphavirus replicon vaccines is determined by many factors including the level of antigen expression and induction of innate immune responses. characterized attenuated alphavirus mutants contain changes to the genomic 5' utr and mutations that result in altered non-structural protein cleavage timing leading to altered levels of antigen expression and interferon (ifn) induction. in an attempt to create more potent replicon vaccines, we engineered a panel of venezuelan equine ...201324210122
sindbis viral vectors target hematopoietic malignant cells.sindbis viral vectors target and inhibit the growth of various solid tumors in mouse models. however, their efficacy against blood cancer has not been well established. here, we show that sindbis vectors infect and efficiently trigger apoptosis in mouse bw5147 malignant hematopoietic t-cells, but only at low levels in human lymphoma and leukemia cells (jurkat, karpas, cem, dhl and jb). the mr 37/67 kd laminin receptor (lamr) has been suggested to be the receptor for sindbis virus. however, jb ce ...201222956041
is minocycline useful for therapy of acute viral encephalitis?minocyline is a tetracycline derivative with anti-inflammatory, anti-apoptotic, and anti-oxidant properties. therapy has proved useful in some experimental models of both noninfectious and infectious neurological diseases and also in clinical trials in humans, including acute traumatic cervical spinal cord injury. in models of viral encephalitis, treatment has shown both beneficial and deleterious effects. in reovirus infection in mice, minocycline delayed the disease, but did not improve either ...201222728256
complete coding sequence and molecular epidemiological analysis of sindbis virus isolates from mosquitoes and humans, finland.sindbis virus (sinv) is an arthropod-borne alphavirus, which causes rash-arthritis, particularly in finland. sinv is transmitted by mosquitoes in finland but thus far no virus has been isolated from mosquitoes. in this study, we report the isolation of the first sinv strain from mosquitoes in finland and its full-length protein-coding sequence. we furthermore describe the full-length coding sequence of six sinv strains previously isolated from humans in finland and from a mosquito in russia. the ...201222647374
prolonged myalgia in sindbis virus infection: case description and in vitro infection of myotubes and myoblasts.sindbis virus (sinv) is a mosquito-borne alphavirus found in eurasia, africa, and oceania. clinical sinv infection is characterized by febrile rash and arthritis and sometimes prolonged arthralgia and myalgia. the pathophysiological mechanisms of musculoskeletal and rheumatic disease caused by sinv are inadequately understood.201222615321
temperature and density-dependent effects of larval environment on aedes aegypti competence for an alphavirus.mosquito larvae experience multiple environmental stressors that may modify how subsequent adults interact with pathogens. we evaluated the effect of larval rearing temperature and intraspecific larval competition on adult mosquito immunity and vector competence for sindbis virus (sinv). aedes aegypti larvae were reared at two intraspecific densities (150 and 300 larvae) at 20° c and 30° c and the adults were fed artificially on citrated bovine blood containing 10(5) plaque forming units of sinv ...201222548549
clinical sindbis alphavirus infection is associated with hla-drb1*01 allele and production of autoantibodies.sindbis virus (sinv) is a mosquito-borne alphavirus found in eurasia, africa, and oceania. clinical sinv infection, characterized by arthropathic disease that may persist for years, is primarily reported in northern europe where the disease has considerable public health importance in endemic areas. the aim of this study was to investigate the role of genetic factors in the susceptibility and outcome of sinv infection and to elucidate the association between sinv infection and autoimmunity.201222523259
sindbis virus infection alters blood feeding responses and deet repellency in aedes aegypti (diptera: culicidae).aedes aegypti (l.) (diptera: culicidae) female mosquitoes infected systemically with sindbis virus (sinv) took longer than uninfected mosquitoes to locate and fully engorge on blood. on days 7 and 14 postexposure, blood feeding took 1.3 and 1.5 times longer in mosquitoes with a disseminated sinv infection, respectively. sinv dissemination did not affect the average weight of unfed ae. aegypti, but did result in a 10 and 12% increase in blood imbibed compared with mosquitoes without a positive si ...201222493862
altered behavioral responses of sindbis virus-infected aedes aegypti (diptera: culicidae) to deet and non-deet based insect repellents.changes in the time to first bite (tfb) and the bloodfeeding behavior of adult female aedes aegypti (l.) mosquitoes following dissemination of sindbis virus (sinv) were observed after exposure to repellents with the active ingredients (ai) deet, picaridin, 2-undecanone (2-u), and oil of lemon eucalyptus. dissemination of sinv significantly decreased (p<0.0001) the tfb of deet (15%) and picaridin (15%) by 46% and 37%, respectively. significant (p<0.0001) changes in activation, probing, and engorg ...201222289669
triple mammalian/yeast/bacterial shuttle vectors for single and combined lentivirus- and sindbis virus-mediated infections of neurons.today, a large variety of viral vectors is available for ectopic gene expression in mammalian cell cultures or in vivo. among them, infection with sindbis virus- or lentivirus-derived constructs is often used to address biological questions or for applications in neuronal therapies. however, cloning of genes of interest is time consuming, since it relies on restriction and ligation, frequently of pcr-generated dna fragments with suitable restriction sites introduced by the primers employed. we h ...201222327349
sindbis virus replicase-based dna vaccine construct encoding fmdv-specific multivalent epitope gene: studies on its immune responses in guinea pigs.foot-and-mouth disease (fmd) is still a perennial global menace affecting livestock health and production. it is imperative to figure out new ways to curb this disease. in this study, a sindbis virus replicase-based dna vaccine, psincmv-vac-meg990, encoding a multivalent epitope gene (representing tandemly linked vp1 c-terminal halves of three foot-and-mouth disease virus (fmdv) serotypes) was constructed. in vitro transfection studies in bhk-21 cells revealed that the construct was able to expr ...201222702835
synthesis and antiviral evaluation of c5-substituted-(1,3-diyne)-2'-deoxyuridines.starting from acetylated 5-ethynyl-2'-deoxyuridine (3), 14 hitherto unknown c5-substituted-(1,3-diyne)-2'-deoxyuridines (with cyclopropyl, hydroxymethyl, methylcyclopentane, p-(substituted)phenyl and disubstituted-phenyl substituents) have been synthesized via a nickel-copper catalyzed c-h activation between two terminal alkynes, in yields ranging from 19% to 67%. their antiviral activities were measured against a large number of dna and rna viruses including herpes simplex virus type 1 and type ...201222578783
membrane targeting of an alpha-like tetravirus replicase is directed by a region within the rna-dependent rna polymerase domain.the members of the family tetraviridae are small positive-sense insect rna viruses that exhibit stringent host specificity and a high degree of tissue tropism, suggesting that complex virus-host interactions are likely to occur during infection and viral replication. the alpha-like replicase of helicoverpa armigera stunt virus (hasv) (genus omegatetravirus) has been proposed to associate with membranes of the endocytic pathway, which is similar to semliki forest virus, sindbis virus and rubella ...201222535773
in vivo administration of recombinant alphavirus into rodents.the alphaviruses semliki forest virus (sfv) and sindbis virus (sin) have been used frequently as expression vectors in vitro and in vivo. usually, these systems consist of replication-deficient vectors that require a helper vector for packaging of recombinant particles. replication-proficient vectors have also been engineered. alphaviral vectors can be used as nucleic-acid-based vectors (dna and rna) or infectious particles. high-titer viral production is achieved in <2 d. the broad host range o ...201222854568
delivery of recombinant alphavirus into hippocampal slice tissue culture.the alphaviruses semliki forest virus (sfv) and sindbis virus (sin) have been used frequently as expression vectors in vitro and in vivo. usually, these systems consist of replication-deficient vectors that require a helper vector for packaging of recombinant particles. replication-proficient vectors have also been engineered. alphaviral vectors can be used as nucleic-acid-based vectors (dna and rna) or infectious particles. high-titer viral production is achieved in <2 d. the broad host range o ...201222854567
generation of recombinant alphaviral vectors.the alphaviruses semliki forest virus and sindbis virus have been used frequently as expression vectors in vitro and in vivo. usually, these systems consist of replication-deficient vectors that require a helper vector for packaging of recombinant particles. replication-proficient vectors have also been engineered. alphaviral vectors can be used as nucleic-acid-based vectors (dna and rna) or infectious particles. high-titer viral production is achieved in <2 d. the broad host range of alphavirus ...201222753600
determination of alphaviral titers.the alphaviruses semliki forest virus and sindbis virus have been used frequently as expression vectors in vitro and in vivo. usually, these systems consist of replication-deficient vectors that require a helper vector for packaging of recombinant particles. replication-proficient vectors have also been engineered. alphaviral vectors can be used as nucleic-acid-based vectors (dna and rna) or infectious particles. the broad host range of alphaviruses facilitates studies in mammalian and nonmammal ...201222753602
purification and concentration of alphavirus.the alphaviruses semliki forest virus and sindbis virus have been used frequently as expression vectors in vitro and in vivo. usually, these systems consist of replication-deficient vectors that require a helper vector for packaging of recombinant particles. replication-proficient vectors have also been engineered. alphaviral vectors can be used as nucleic-acid-based vectors (dna and rna) or infectious particles. high-titer viral production is achieved in <2 d. the broad host range of alphavirus ...201222753601
[preparation and identification of a recombinant hepatitis c virus (hcv) based on sindbis virus vector].to construct the recombinant virus-like particles containing hcv envelope glycoprotein e1e2 based on sindbis virus vector.201223002557
67 kda laminin receptor: structure, function and role in cancer and infection.the 67 kda high affinity laminin receptor (67lr) is a non integrin cell surface receptor for the extracellular matrix whose expression is increased in neoplastic cells and directly correlates with an enhanced invasive and metastatic potential. 67lr derives from homo- or hetero-dimerization of a 37 kda cytosolic precursor (37lrp), by fatty acid acylation. interestingly, 37lrp is a multifunctional protein involved in the translational machinery and has also been found in the nucleus, where it is t ...201223042000
arthritogenic alphaviruses--an overview.mosquito-transmitted alphaviruses causing human rheumatic disease are globally distributed and include chikungunya virus, ross river virus, barmah forest virus, sindbis virus, o'nyong-nyong virus and mayaro virus. these viruses cause endemic disease and, occasionally, large epidemics; for instance, the 2004-2011 chikungunya epidemic resulted in 1.4-6.5 million cases, with imported cases reported in nearly 40 countries. the disease is usually self-limiting and characterized by acute and chronic s ...201222565316
chikungunya virus and the safety of plasma products.chikungunya virus (chikv) outbreaks were previously restricted to parts of africa, indian ocean islands, south asia, and southeast asia. in 2007, however, the first autochthonous chikv transmission was reported in europe. high-level viremia, a mosquito vector that is also present in large urban areas of europe and america, and uncertainty around the resistance of this alphavirus toward physiochemical inactivation processes raised concerns about the safety of plasma derivatives. to verify the saf ...201222339168
prostratin and 12-o-tetradecanoylphorbol 13-acetate are potent and selective inhibitors of chikungunya virus replication.a chemical study of the vietnamese plant species trigonostemon howii led to the isolation of a new tigliane-type diterpenoid, trigowiin a (1), along with several known coumarins and phenylpropanoids. the planar structure and the relative configuration of compound 1 were elucidated based on spectroscopic analysis, including 1d- and 2d-nmr experiments, mass spectrometry, and comparison with literature data. trigowiin a (1) exhibited moderate antiviral activity in a virus-cell-based assay for chiku ...201223215460
antiviral chlorinated daphnane diterpenoid orthoesters from the bark and wood of trigonostemon cherrieri.the chemical study of the bark and the wood of trigonostemon cherrieri, a rare endemic plant of new caledonia, led to the isolation of a series of highly oxygenated daphnane diterpenoid orthoesters (ddo) bearing an uncommon chlorinated moiety: trigocherrins a-f and trigocherriolides a-d. herein, we describe the isolation and structure elucidation of the ddo (trigocherrins b-f and trigocherriolides a-d). we also report the antiviral activity of trigocherrins a, b and f (1, 2 and 6) and trigocherr ...201222938995
hepatitis c virus and cellular stress response: implications to molecular pathogenesis of liver diseases.infection with hepatitis c virus (hcv) is a leading risk factor for chronic liver disease progression, including steatosis, cirrhosis, and hepatocellular carcinoma. with approximately 3% of the human population infected worldwide, hcv infection remains a global public health challenge. the efficacy of current therapy is still limited in many patients infected with hcv, thus a greater understanding of pathogenesis in hcv infection is desperately needed. emerging lines of evidence indicate that hc ...201223202463
inhibitory effects of crude extracts from some edible thai plants against replication of hepatitis b virus and human liver cancer cells.edible plants such as cratoxylum formosum (jack) dyer, curcumin longa lin, momordica charantia lin and moringa oleifera lam have long been believed in thai culture to relieve ulcers and the symptoms of liver disease. however, little is known about their anti-liver cancer properties and antiviral activity against hepatitis b virus (hbv). the aim of this study was to investigate the anti-liver cancer and anti-hbv activities of crude extracts from these edible plants on human liver cancer cells.201223216691
immunization of mice with recombinant mosquito salivary protein d7 enhances mortality from subsequent west nile virus infection via mosquito bite.mosquito salivary proteins (msps) modulate the host immune response, leading to enhancement of arboviral infections. identification of proteins in saliva responsible for immunomodulation and counteracting their effects on host immune response is a potential strategy to protect against arboviral disease. we selected a member of the d7 protein family, which are among the most abundant and immunogenic in mosquito saliva, as a vaccine candidate with the aim of neutralizing effects on the mammalian i ...201223236530
cell-type specific requirements for thiol/disulfide exchange during hiv-1 entry and infection.the role of disulfide bond remodeling in hiv-1 infection is well described, but the process still remains incompletely characterized. at present, the data have been predominantly obtained using established cell lines and/or cxcr4-tropic laboratory-adapted virus strains. there is also ambiguity about which disulfide isomerases/reductases play a major role in hiv-1 entry, as protein disulfide isomerase (pdi) and/or thioredoxin (trx) have emerged as the two enzymes most often implicated in this pro ...201223206338
vesicular stomatitis virus as a flexible platform for oncolytic virotherapy against cancer.oncolytic virus (ov) therapy is an emerging anti-cancer approach that utilizes viruses to preferentially infect and kill cancer cells, while not harming healthy cells. vesicular stomatitis virus (vsv) is a prototypic non-segmented, negative-strand rna virus with inherent ov qualities. antiviral responses induced by type i interferon pathways are believed to be impaired in most cancer cells, making them more susceptible to vsv than normal cells. several other factors make vsv a promising ov candi ...201223052398
reverse transcription loop-mediated isothermal amplification for rapid detection of japanese encephalitis virus in swine and mosquitoes.japanese encephalitis (je) can infect many agriculturally important animals and humans, and has a high incidence in asia. one of the natural hosts of the mosquito-borne je virus (jev) is domestic pigs, which act as amplifier hosts. porcine infection results in fatal encephalitis, abortion, and stillbirth in pregnant sows, and hypospermia in boars. in this study, a rapid jev detection method for swine and mosquitoes was developed based on reverse transcription loop-mediated isothermal amplificati ...201223176446
rna interference as a cellular defense mechanism against the dna virus baculovirus.in insects, the rna interference (rnai) pathway plays a major role in antiviral responses, as shown against many rna viruses. the response includes the cleavage of double-stranded rna genome or intermediates, produced during replication, into viral short interfering rnas (v-sirnas). using deep sequencing, we found that a large number of small reads of ∼20 nucleotides from helicoverpa armigera larvae infected with helicoverpa armigera single nucleopolyhedrovirus (hasnpv) were mapped to certain op ...201223055564
gamma interferon (ifn-γ) receptor restricts systemic dengue virus replication and prevents paralysis in ifn-α/β receptor-deficient mice.we previously reported that mice lacking alpha/beta and gamma interferon receptors (ifn-α/βr and -γr) uniformly exhibit paralysis following infection with the dengue virus (denv) clinical isolate pl046, while only a subset of mice lacking the ifn-γr alone and virtually no mice lacking the ifn-α/βr alone develop paralysis. here, using a mouse-passaged variant of pl046, strain s221, we show that in the absence of the ifn-α/βr, signaling through the ifn-γr confers approximately 140-fold greater res ...201222973027
longitudinal analysis of the human antibody response to chikungunya virus infection: implications for serodiagnosis and vaccine development.chikungunya virus (chikv) is an alphavirus which causes chronic and incapacitating arthralgia in humans. although previous studies have shown that antibodies against the virus are produced during and after infection, the fine specificity of the antibody response against chikv is not known. here, using plasma from patients at different times postinfection, we characterized the antibody response against various proteins of the virus. we have shown that the e2 and e3 glycoproteins and the capsid an ...201223015702
foot-and-mouth disease virus induces autophagosomes during cell entry via a class iii phosphatidylinositol 3-kinase-independent pathway.autophagy is an intracellular pathway that can contribute to innate antiviral immunity by delivering viruses to lysosomes for degradation or can be beneficial for viruses by providing specialized membranes for virus replication. here, we show that the picornavirus foot-and-mouth disease virus (fmdv) induces the formation of autophagosomes. induction was dependent on atg5, involved processing of lc3 to lc3ii, and led to a redistribution of lc3 from the cytosol to punctate vesicles indicative of a ...201222993157
involvement of autophagy in coronavirus replication.coronaviruses are single stranded, positive sense rna viruses, which induce the rearrangement of cellular membranes upon infection of a host cell. this provides the virus with a platform for the assembly of viral replication complexes, improving efficiency of rna synthesis. the membranes observed in coronavirus infected cells include double membrane vesicles. by nature of their double membrane, these vesicles resemble cellular autophagosomes, generated during the cellular autophagy pathway. in a ...201223202545
release of dengue virus genome induced by a peptide inhibitor.dengue virus infects approximately 100 million people annually, but there is no available therapeutic treatment. the mimetic peptide, dn59, consists of residues corresponding to the membrane interacting, amphipathic stem region of the dengue virus envelope (e) glycoprotein. this peptide is inhibitory to all four serotypes of dengue virus, as well as other flaviviruses. cryo-electron microscopy image reconstruction of dengue virus particles incubated with dn59 showed that the virus particles were ...201223226444
il-1β signaling promotes cns-intrinsic immune control of west nile virus infection.west nile virus (wnv) is an emerging flavivirus capable of infecting the central nervous system (cns) and mediating neuronal cell death and tissue destruction. the processes that promote inflammation and encephalitis within the cns are important for control of wnv disease but, how inflammatory signaling pathways operate to control cns infection is not defined. here, we identify il-1β signaling and the nlrp3 inflammasome as key host restriction factors involved in viral control and cns disease as ...201223209411
complex modulation of the aedes aegypti transcriptome in response to dengue virus infection.dengue fever is the most important arboviral disease world-wide, with aedes aegypti being the major vector. interactions between the mosquito host and dengue viruses (denv) are complex and vector competence varies among geographically-distinct ae. aegypti populations. additionally, dengue is caused by four antigenically-distinct viral serotypes (denv1-4), each with multiple genotypes. each virus genotype interacts differently with vertebrate and invertebrate hosts. analyses of alterations in mos ...201223209765
genotypic and phenotypic characterization of chikungunya virus of different genotypes from malaysia.mosquito-borne chikungunya virus (chikv) has recently re-emerged globally. the epidemic east/central/south african (ecsa) strains have spread for the first time to asia, which previously only had endemic asian strains. in malaysia, the ecsa strain caused an extensive nationwide outbreak in 2008, while the asian strains only caused limited outbreaks prior to this. to gain insight into these observed epidemiological differences, we compared genotypic and phenotypic characteristics of chikv of asia ...201223209750
host mtorc1 signaling regulates andes virus replication.hantavirus pulmonary syndrome (hps) is a severe respiratory disease characterized by pulmonary edema, with fatality rates of 35 to 45%. disease occurs following infection with pathogenic new world hantaviruses, such as andes virus (andv), which targets lung microvascular endothelial cells. during replication, the virus scavenges 5'-m(7)g caps from cellular mrna to ensure efficient translation of viral proteins by the host cell cap-dependent translation machinery. in cells, the mammalian target o ...201223135723
the west nile virus capsid protein blocks apoptosis through a phosphatidylinositol 3-kinase-dependent mechanism.west nile virus (wnv) is a mosquito-transmitted pathogen that can cause serious disease in humans. our laboratories are focused on understanding how interactions between wnv proteins and host cells contribute to virus replication and pathogenesis. wnv replication is relatively slow, and on the basis of earlier studies, the virus appears to activate survival pathways that delay host cell death during virus replication. the wnv capsid is the first viral protein produced in infected cells; however, ...201223115297
induction of stress granule-like structures in vesicular stomatitis virus-infected cells.previous studies from our laboratory revealed that cellular poly(c) binding protein 2 (pcbp2) downregulates vesicular stomatitis virus (vsv) gene expression. we show here that vsv infection induces the formation of granular structures in the cytoplasm containing cellular rna-binding proteins, including pcbp2, t-cell-restricted intracellular antigen 1 (tia1), and tia1-related protein (tiar). depletion of tia1 via small interfering rnas (sirnas), but not depletion of tiar, results in enhanced vsv ...201223077311
long-distance rna-rna interactions in the coronavirus genome form high-order structures promoting discontinuous rna synthesis during transcription.coronavirus (cov) transcription requires a high-frequency recombination process that links newly synthesized minus-strand subgenomic rna copies to the leader region, which is present only once, at the 5' end of the genome. this discontinuous rna synthesis step is based on the complementarity between the transcription-regulating sequences (trss) at the leader region and those preceding each gene in the nascent minus-strand rna. furthermore, the template switch requires the physical proximity of r ...201223055566
enterovirus 71 uses cell surface heparan sulfate glycosaminoglycan as an attachment receptor.enterovirus 71 (ev-71) infections are usually associated with mild hand, foot, and mouth disease in young children but have been reported to cause severe neurological complications with high mortality rates. to date, four ev-71 receptors have been identified, but inhibition of these receptors by antagonists did not completely abolish ev-71 infection, implying that there is an as yet undiscovered receptor(s). since ev-71 has a wide range of tissue tropisms, we hypothesize that ev-71 infections ma ...201223097443
tailored hiv-1 vectors for genetic modification of primary human dendritic cells and monocytes.monocyte-derived dendritic cells (mddcs) play a key role in the regulation of the immune system and are the target of numerous gene therapy applications. the genetic modification of mddcs is possible with human immunodeficiency virus type 1 (hiv-1)-derived lentiviral vectors (lvs) but requires high viral doses to bypass their natural resistance to viral infection, and this in turn affects their physiological properties. to date, a single viral protein is able to counter this restrictive phenotyp ...201223077304
a novel inhibitor of dengue virus replication that targets the capsid protein.dengue viruses (denv) infect 50 to 100 million people worldwide per year, of which 500,000 develop severe life-threatening disease. this mosquito-borne illness is endemic in most tropical and subtropical countries and has spread significantly over the last decade. while there are several promising vaccine candidates in clinical trials, there are currently no approved vaccines or therapeutics available for treatment of dengue infection. here, we describe a novel small-molecule compound, st-148, t ...201223070172
interplay between viruses and host mrna degradation.messenger rna degradation is a fundamental cellular process that plays a critical role in regulating gene expression by controlling both the quality and the abundance of mrnas in cells. naturally, viruses must successfully interface with the robust cellular rna degradation machinery to achieve an optimal balance between viral and cellular gene expression and establish a productive infection in the host. in the past several years, studies have discovered many elegant strategies that viruses have ...201223274304
the folded and disordered domains of human ribosomal protein sa have both idiosyncratic and shared functions as membrane receptors.the human rpsa [ribosomal protein sa; also known as lamr1(laminin receptor 1)] belongs to the ribosome but is also a membrane receptor for laminin, growth factors, prion, pathogens and the anticarcinogen egcg (epigallocatechin-gallate). it contributes to the crossing of the blood-brain barrier by neurotropic viruses and bacteria, and is a biomarker of metastasis. rpsa includes an n-terminal domain, which is folded and homologous to the prokaryotic rps2, and a c-terminal extension, which is intri ...201223137297
mouse macrophage innate immune response to chikungunya virus infection.infection with chikungunya alphavirus (chikv) can cause severe arthralgia and chronic arthritis in humans with persistence of the virus in perivascular macrophages of the synovial membrane by mechanisms largely ill-characterized.201223253140
broad rna interference-mediated antiviral immunity and virus-specific inducible responses in drosophila.the fruit fly drosophila melanogaster is a good model to unravel the molecular mechanisms of innate immunity and has led to some important discoveries about the sensing and signaling of microbial infections. the response of drosophila to virus infections remains poorly characterized and appears to involve two facets. on the one hand, rna interference involves the recognition and processing of dsrna into small interfering rnas by the host rnase dicer-2 (dcr-2), whereas, on the other hand, an indu ...201223255357
macrophages, inflammation, and tumor suppressors: arf, a new player in the game.the interaction between tumor progression and innate immune system has been well established in the last years. indeed, several lines of clinical evidence indicate that immune cells such as tumor-associated macrophages (tams) interact with tumor cells, favoring growth, angiogenesis, and metastasis of a variety of cancers. in most tumors, tams show properties of an alternative polarization phenotype (m2) characterized by the expression of a series of chemokines, cytokines, and proteases that prom ...201223316105
inflammatory monocytes and the pathogenesis of viral encephalitis.monocytes are a heterogeneous population of bone marrow-derived cells that are recruited to sites of infection and inflammation in many models of human diseases, including those of the central nervous system (cns). ly6chi/ccr2(hi) inflammatory monocytes have been identified as the circulating precursors of brain macrophages, dendritic cells and arguably microglia in experimental autoimmune encephalomyelitis; alzheimer's disease; stroke; and more recently in cns infection caused by herpes simplex ...201223244217
replication of west nile virus, rabensburg lineage in mammalian cells is restricted by temperature.the genus flavivirus currently consists of approximately 80 single-strand positive-sense rna viruses. these replicate in a range of hosts including myriad vertebrate, insect, and tick species. as a consequence of this broad host range, the majority of flaviviruses can be propagated in most vertebrate and insect cell cultures. this ability to infect arthropods and vertebrates usually is essential for maintenance of these viruses in nature. but recently, there has been the discovery of a number of ...201223241081
proteomics-based methods for discovery, quantification, and validation of protein-protein interactions. 201223157382
hyperresponsiveness of mice deficient in plasma-secreted sphingomyelinase reveals its pivotal role in early phase of host response.plasma secretion of acid sphingomyelinase is a hallmark of cellular stress response resulting in the formation of membrane embedded ceramide-enriched lipid rafts and the reorganization of receptor complexes. consistently, decompartmentalization of ceramide formation from inert sphingomyelin has been associated with signaling events and regulation of the cellular phenotype. herein, we addressed the question of whether the secretion of acid sphingomyelinase is involved in host response during seps ...201223230083
a new rabies vaccine based on a recombinant orf virus (parapoxvirus) expressing the rabies virus glycoprotein.the present study describes the generation of a new orf virus (orfv) recombinant, d1701-v-rabg, expressing the rabies virus (rabv) glycoprotein that is correctly presented on the surface of infected cells without the need of replication or production of infectious recombinant virus. one single immunization with recombinant orfv can stimulate high rabv-specific virus-neutralizing antibody (vna) titers in mice, cats, and dogs, representing all nonpermissive hosts for the orfv vector. the protectiv ...201223175365
dicer-2- and piwi-mediated rna interference in rift valley fever virus-infected mosquito cells.rift valley fever virus (rvfv) is a phlebovirus (bunyaviridae family) transmitted by mosquitoes. it infects humans and ruminants, causing dramatic epidemics and epizootics in africa, yemen, and saudi arabia. while recent studies demonstrated the importance of the nonstructural protein nss as a major component of virulence in vertebrates, little is known about infection of mosquito vectors. here we studied rvfv infection in three different mosquito cell lines, aag2 cells from aedes aegypti and u4 ...201223175368
the gef1 proton-chloride exchanger affects tombusvirus replication via regulation of copper metabolism in yeast.replication of plus-strand rna viruses [(+)rna viruses] is performed by viral replicases, whose function is affected by many cellular factors in infected cells. in this paper, we demonstrate a surprising role for gef1p proton-chloride exchanger in replication of tomato bushy stunt virus (tbsv) model (+)rna virus. a genetic approach revealed that gef1p, which is the only proton-chloride exchanger in saccharomyces cerevisiae, is required for tbsv replication in the yeast model host. we also show t ...201223192874
dugbe virus ovarian tumour domain interferes with ubiquitin/isg15-regulated innate immune cell signalling.the ovarian tumour (otu) domain of the nairovirus l protein has been shown to remove ubiquitin and interferon-stimulated gene 15 protein (isg15) from host cell proteins, which is expected to have multiple effects on cell signalling pathways. we have confirmed that the otu domain from the l protein of the apathogenic nairovirus dugbe virus has deubiquitinating and deisgylating activity and shown that, when expressed in cells, it is highly effective at blocking the tnf-α/nf-κb and interferon/jak/s ...201223136361
gene expression studies of host response to salmonid alphavirus subtype 3 experimental infections in atlantic salmon.salmonid alphavirus subtype-3 (sav-3) infection in atlantic salmon is exclusively found in norway. the salmonid alphaviruses have been well characterized at the genome level but there is limited information about the host-pathogen interaction phenomena. this study was undertaken to characterize the replication and spread of sav-3 in internal organs of experimentally infected atlantic salmon and the subsequent innate and adaptive immune responses. in addition, suitability of a cohabitation challe ...201223116479
zinc finger antiviral protein inhibits murine gammaherpesvirus 68 m2 expression and regulates viral latency in cultured cells.zinc finger antiviral protein (zap) is a host factor that specifically inhibits the replication of certain viruses by binding to specific viral mrnas and repressing mrna expression. here we report that zap inhibits expression of murine gammaherpesvirus 68 (mhv-68) m2, which plays important roles in establishment and maintenance of viral latency. downregulation of endogenous zap in cells harboring latent mhv-68 promoted lytic replication of the virus. these results suggest that zap inhibits m2 ex ...201222951821
autophagy as a stress-response and quality-control mechanism: implications for cell injury and human disease.autophagy, a vital catabolic process that degrades cytoplasmic components within the lysosome, is an essential cytoprotective response to pathologic stresses that occur during diseases such as cancer, ischemia, and infection. in addition to its role as a stress-response pathway, autophagy plays an essential quality-control function in the cell by promoting basal turnover of long-lived proteins and organelles, as well as by selectively degrading damaged cellular components. this homeostatic funct ...201223072311
making connections in insect innate immunity. 201223100537
transient activation of the pi3k-akt pathway by hepatitis c virus to enhance viral entry.the pi3k-akt signaling pathway plays an important role in cell growth and metabolism. here we report that hepatitis c virus (hcv) transiently activates the pi3k-akt pathway. this activation was observed as early as 15 min postinfection, peaked by 30 min, and became undetectable at 24 h postinfection. the activation of akt could also be mediated by uv-inactivated hcv, hcv pseudoparticle, and the ectodomain of the hcv e2 envelope protein. because antibodies directed against cd81 and claudin-1, but ...201223095753
autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation.autophagy is a cell biological pathway affecting immune responses. in vitro, autophagy acts as a cell-autonomous defense against mycobacterium tuberculosis, but its role in vivo is unknown. here we show that autophagy plays a dual role against tuberculosis: antibacterial and anti-inflammatory. m. tuberculosis infection of atg5(fl/fl) lysm-cre(+) mice relative to autophagy-proficient littermates resulted in increased bacillary burden and excessive pulmonary inflammation characterized by neutrophi ...201223093667
in vivo gene transfer targeting in pancreatic adenocarcinoma with cell surface antigens.pancreatic ductal adenocarcinoma is a deadly malignancy resistant to current therapies. it is critical to test new strategies, including tumor-targeted delivery of therapeutic agents. this study tested the possibility to target the transfer of a suicide gene in tumor cells using an oncotropic lentiviral vector.201223088623
infection by chikungunya virus modulates the expression of several proteins in aedes aegypti salivary glands.arthropod-borne viral infections cause several emerging and resurging infectious diseases. among the diseases caused by arboviruses, chikungunya is responsible for a high level of severe human disease worldwide. the salivary glands of mosquitoes are the last barrier before pathogen transmission.201223153178
demographic consequences of predators on prey: trait and density mediated effects on mosquito larvae in containers.predators may affect prey population growth and community diversity through density mediated lethal and trait mediated non-lethal effects that influence phenotypic traits of prey. we tested experimentally the roles of thinning the density of prey (lethality) in the absence of predator cues and density and trait mediated effects (lethality + intimidation) of predatory midge corethrella appendiculata on competing native and invasive mosquito prey. predator-mediated reductions in prey and density r ...201223152748
modulation of hepatitis c virus rna abundance and virus release by dispersion of processing bodies and enrichment of stress granules.components of cytoplasmic processing bodies (p-bodies) and stress granules can be subverted during viral infections to modulate viral gene expression. because hepatitis c virus (hcv) rna abundance is regulated by p-body components such as microrna mir-122, argonaute 2 and rna helicase rck/p54, we examined whether hcv infection modulates p-bodies and stress granules during viral infection. it was discovered that hcv infection decreased the number of p-bodies, but induced the formation of stress g ...201223141719
dendritic cell-directed vaccination with a lentivector encoding psca for prostate cancer in mice.many studies have demonstrated that prostate stem cell antigen (psca) is an attractive target for immunotherapy based on its overexpression in prostate tumor tissue, especially in some metastatic tissues. in this study, we evaluated dendritic cell (dc)-directed lentiviral vector (dclv) encoding murine psca (dclv-psca) as a novel tumor vaccine for prostate cancer in mouse models. we showed that dclv-psca could preferentially deliver the psca antigen gene to dc-sign-expressing 293t cells and bone ...201223139820
apoptosis in mosquito salivary glands: sindbis virus-associated and tissue homeostasis.apoptosis is observed during a spectrum of conditions including exogenous virus infection and endogenous cellular turnover. adult female aedes albopictus mosquitoes challenged with increasing titres of sindbis virus (sinv) via intrathoracic inoculation demonstrated that the injection dosage did not result in significantly different levels of virus growth or mosquito survival at day 10 post-infection. tissues probed for apoptosis using an in situ tunel assay revealed sinv-associated apoptotic cel ...201222894924
expression of plasmid-based shrna against the e1 and nsp1 genes effectively silenced chikungunya virus replication.chikungunya virus (chikv) is a re-emerging alphavirus that causes chikungunya fever and persistent arthralgia in humans. currently, there is no effective vaccine or antiviral against chikv infection. therefore, this study evaluates whether rna interference which targets at viral genomic level may be a novel antiviral strategy to inhibit the medically important chikv infection.201223056297
vipr hmm: a hidden markov model for detecting recombination with microbial detection microarrays.current methods in diagnostic microbiology typically focus on the detection of a single genomic locus or protein in a candidate agent. the presence of the entire microbe is then inferred from this isolated result. problematically, the presence of recombination in microbial genomes would go undetected unless other genomic loci or protein components were specifically assayed. microarrays lend themselves well to the detection of multiple loci from a given microbe; furthermore, the inherent nature o ...201223044542
autophagy and selective deployment of atg proteins in antiviral defense.autophagy is an evolutionarily ancient process eukaryotic cells utilize to remove and recycle intracellular material in order to maintain cellular homeostasis. in metazoans, the autophagy machinery not only functions in this capacity but also has evolved to perform a diverse repertoire of intracellular transport and regulatory functions. in response to virus infections, the autophagy machinery degrades viruses, shuttles viral pathogen-associated molecular patterns to endosomes containing toll-li ...201223042773
testing of novel dengue virus 2 vaccines in african green monkeys: safety, immunogenicity, and efficacy.the immunogenicity and safety of three novel host-range vaccines containing deletions in the transmembrane domain of dengue virus serotype 2 (dv2) e glycoprotein were evaluated in african green monkeys. the shorter transmembrane domains are capable of functionally spanning an insect but not a mammalian cell membrane, resulting in production of viral mutants that have reduced infectivity in mammalian hosts but efficient growth in insect cells. groups of four monkeys received one dose each of test ...201222890035
living on the edge with too many mouths to feed: why dopamine neurons die.although genes, protein aggregates, environmental toxins, and other factors associated with parkinson's disease (pd) are widely distributed in the nervous system and affect many classes of neurons, a consistent feature of pd is the exceptional and selective vulnerability of dopamine (da) neurons of the snc. what is it about these neurons, among all other neurons in the brain, that makes them so susceptible in pd? we hypothesize that a major contributory factor is the unique cellular architecture ...201223008164
pathogenic characterization of a cervical lymph node derived from a patient with kawasaki disease.kawasaki disease (kd) is the most common cause of multisystem vasculitis in childhood. although cervical lymphadenitis is one of the major symptoms in kd, lymph node biopsy is rarely performed, because kd is usually diagnosed by clinical symptoms. a cervical lymph node biopsy was taken from a girl aged 1 year and 8 months who had suspected lymphoma, but she was diagnosed with kd after the biopsy. the cervical lymph node specimen was analyzed with multivirus real-time pcr that can detect >160 vir ...201223071864
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